Recent results suggest that hyperthermia combined with X or gamma radiation may simulate the effects of high L.E.T. radiation in that the radiation sensitivity of hypoxic cells is increased. If this observation is confirmed and can be exploited clinically, very likely the radiation therapist can improve greatly the yield of tumor cures. Thus, patients may derive the expected benefits of high L.E.T. radiotherapy without the expense necessary to construct and maintain sources of high L.E.T. particles. On the other hand, combined treatment with hyperthermia plus high L.E.T. radiation may provide yet further increased benefits. To be clinically useful, heat must be delivered to some depth in tissue while, at the same time, the surface tissue (skin) is not heated significantly. This is necessary in order to maintain a therapeutic margin between the tumor and the incidentially irradiated normal tissues. Two modalites now available for heating deeply-seated lesions are ultrasound and microwaves. We propose to perform an in-depth study of the interaction of: 1) agents which cause heating (thermal heat, ultrasound, and microwaves) and 2) ionizing radiations of both low (250 kvp X-rays) and high (fast neutrons) L.E.T. Cultured cells of three different mammalian lines will be used; cell populations will be synchronized where appropriate. The experiments will be performed under conditions of hypoxia as well as normal oxygenation. Both cellular (proliferity integrity) and molecular (production and repair of DNA single strand breaks) effects will be measured. The results of these experiments will provide valuable information towards the evaluation of the question, "Does hyperthermia combined with low L.E.T. radiation truly simulate high L.E.T. radiation?" These data will help to establish a biological base from which rational clinical trials can be formulated.